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Biomedical subjects

Y Kawarada

Publications and source records attributed to Y Kawarada.

At least 37 records · Page 2Linked to original sources

Lithium affects the reactivities of GalNAcalpha1-3GalNAc-lipid and fibrinopeptide A in mice.

The relationship between lithium and the reactivities of GalNAcalpha1-3GalNAc-lipid and fibrinopeptide A were investigated in mice. Lithium strongly decreased glycolipid reactivity and slightly increased peptide reactivity in a dose- and time-dependent manner. These substances showed antidepressive behavioral effects in mice via different neurological activities. This many suggest a mechanism of two different clinical effects of lithium: one of which is a strong antimanic effect and one of which is a weak antidepressive effect.

Animals↗

[Hepatopancreatoduodenectomy (HPD)].

Since the mid-1980s, simultaneous major resection of the liver and the pancreatic head, so-called HPD, has been performed in Japan to improve the survival rate of patients with advanced biliary tract carcinoma. We conducted a study of HPD in dogs in our laboratory from 1986 to 1989 and found that 75% died following 70% hepatectomy with more than 92% pancreatectomy and that only 25% survived. The main cause of death was liver failure. A clinical review of the operative procedures and the outcome of HPD was performed by Mizumoto et al. in our department in 1989. They collected data on 241 patients who underwent HPD for advanced biliary tract carcinoma throughout Japan. The postoperative morbidity and mortality rates after HPD were higher than after other major surgeries. The prognosis after HPD has improved in recent years because of preservation of adequate hepatic or pancreatic parenchyma, improvements in surgical technique, and strict perioperative care. Therefore we plan to review the operative procedures and outcome of HPD again in 2000.

Female↗

[Optimal lymph node dissection for carcinoma of the biliary tract].

To clarify the optimal lymph node dissection for carcinoma of the biliary tract, we analyzed the mode of lymphatic spread in 86 resected cases with carcinoma of the gallbladder and 139 with carcinoma of the extrahepatic bile duct, and investigated long-term results after resection based on the degree of lymph node metastasis. Of the 86 patients with carcinoma of the gallbladder, 62 (72.1%) had lymph node metastasis. Patients with m and mp tumors (n = 9) had no lymph node metastasis, whereas ss tumors (n = 13) had 23.1% lymph node metastasis. Those with se, si tumors (n = 64) had greater lymph node involvement (92.2%). In 4 patients with advanced carcinomas (ss or more) who survived more than 5 years, only one (limited to periportal lymph nodes) of them had lymph node metastasis. Of the 139 patients with carcinoma of the extrahepatic bile duct, 58 (41.7%) had lymph node metastasis. There was no lymph node metastasis in 15 patients with m or fm tumors. The frequency of metastasis in the ss (n = 39) and se, si (n = 85) tumors was 17.9% and 60.0%, respectively. Twenty-four patients with advanced tumors survived more than 5 years. Curative resection was achieved in all 24 and lymph node metastasis was n0 in 19, n1 in 4 and n2 in 1 patients. Satisfactory long-term result can be achieved in carcinoma of the biliary tract after resection when lymph node metastasis is limited to nodes in the hepatoduodenal ligament. In view of our surgical results and the lymphatic drainage system of the biliary tract, systemic dissection of the regional lymph nodes, including periportal, posterior pancreato-duodenal, and celiac nodes, is necessary in patients with N0-N2 (limited to lymph nodes in the hapatoduodenal ligament) tumors in whom it contributes to good prognosis.

Biliary Tract Neoplasms↗

Multi-impulsivity of Japanese patients with eating disorders: primary and secondary impulsivity.

Several studies have noted that multi-impulsive bulimia nervosa tends to be refractory to treatment. However, it is not known whether these impulsivities are an expression of more fundamental psychopathology or simply the consequence of chaotic eating behaviors. Studies of the temporal relationship between the onset of eating disorder and the occurrence of impulsive behaviors will facilitate a better understanding of these issues. Subjects consisted of 60 patients with anorexia nervosa restricting type (AN-R), 62 patients with anorexia nervosa binge-eating/purging type (AN-BP), 114 patients with bulimia nervosa purging type (BN) and 66 control subjects. Impulsive behaviors and childhood traumatic experiences were assessed by self-report questionnaire. Multi-impulsivity (defined by at least three of the following: heavy regular alcohol drinking; suicide attempt; self-mutilation; repeated shoplifting of items other than food; sexual relationships with persons not well known to the subject) was found in 2% of AN-R, 11% of AN-BP, 18% of BN and 2% of control subjects. Eighty percent of BN patients with multi-impulsivity had a history of suicide attempts or self-mutilation history prior to the onset of bulimia nervosa. In BN patients, there tended to be a relationship between childhood parental loss or borderline personality disorder and multi-impulsivity. In conclusion, primary impulsivity (chronological prior occurrence of impulsive behaviors) does exist even in a very different culture, although the number of patients of this type is very limited.

Adult↗

Expression of matrix metalloproteinases and related tissue inhibitors in the cyst fluids of ovarian mucinous neoplasms.

OBJECTIVES AND METHODS: The growth of an ovarian cystic neoplasm often involves its invasion into and destruction of the extracellular matrix. We examined neoplastic cysts of ovarian mucinous tumors for the presence of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) using zymography (in situ zymography, gelatin zymography, and casein zymography) and enzyme-linked immunosorbent assay. RESULTS: Matriolytic activity was detected within the cystic contents and cytoplasm of the lining epithelial cells of the cyst by in situ zymography. This intracystic matriolytic activity was thought to originate mainly in the epithelial cells. The activated form of MMP-9 was seen in all carcinoma and borderline fluids and in 7 of 15 adenomas. The concentration of MMP-9 was higher in carcinoma fluids than in borderline and adenoma fluids (P < 0.05). TIMP-1, which specifically binds to MMP-9, was also higher in carcinoma and borderline fluids than in adenoma fluids (P < 0.05). MMP-2 activity was nearly ubiquitously present in all cyst fluids, irrespective of the fluid's histologic category. The amount of MMP-2 was highest in the carcinoma category, although not to a statistically significant degree. TIMP-2, a specific inhibitor for MMP-2, was significantly lower in the borderline category than in the adenoma category. The molar ratios of TIMP-1/MMP-9 (not significant) and TIMP-2/MMP-2 (P < 0.05) were higher in the adenoma category. Expressions of trypsin, MMP-7, and MMP-9 were generally higher in carcinoma and borderline fluids than in adenoma fluids. CONCLUSIONS: These observations indicate the importance of ovarian cystic fluids for analyzing tumor-associated matriolytic activities. The findings suggest that these matriolytic enzymes, together with the presence of their inhibitors, play an important role in the growth of ovarian mucinous tumors.

Adenocarcinoma, Mucinous↗

Surgical treatment for hilar cholangiocarcinoma.

From September 1976 to February 1998, we experienced 75 resected patients with hilar cholangiocarcinoma. Curative resection was performed in 45 patients (60.0%), with a cumulative 5-year survival rate of 39.8%. In this retrospective study, we compared therapeutic outcomes in these 75 patients according to the period during which they were treated; (1) 12 patients in the early period (September 1976 to August 1981) chiefly treated by bile duct resection, (2) 50 patients in the middle period, September 1981 to August 1994, chiefly treated by aggressive surgical procedures with extensive hepatectomy plus caudate lobe resection, and (3) 13 patients in the late period, September 1994 to February 1998, during which percutaneous transhepatic portal embolization was introduced to increase the safety and curability of extended hepatectomy, and limited hepatectomy was selected according to tumor spread. In the late period, total resection of the caudate lobe was done in all patients, with the aim being thorough resection of cancer cells in the caudate lobe. The curative resection rates were 16.7% in the early period, 64.0% in the middle period, and 84.6% in the late period, showing an improvement year-by-year (P<0.05; early period vs middle period and late period). All patients in the early period died within 2 years of resection, whereas the 5-year survival rate in the middle period was 24.4%, significantly improved (P<0.05) compared with the early period. The 1- and 3-year survival rates of 84.6% and 58.0%, respectively, in the late period, show an even greater improvement in outcome.

Adult↗

Anatomy of the hepatic hilar area: the plate system.

To surgically manage hilar bile duct carcinoma successfully, it is important to be familiar with the principal anatomical variations of the biliary and vascular components of the plate system in the hepatic hilar area, because all the variations in the bile ducts and vessels occur in the plate system. The plate system consists of bile ducts and blood vessels surrounded by a sheath. There are three plates in the hilar area: the hilar plate, the cystic plate, and the umbilical plate. The bile duct and blood vessel branches penetrate the plate system and form Glisson's capsule in all segments of the liver, except for the medial segment. The right hepatic duct is usually (in 53%-72% of individuals) formed by the union of the anterior segmental duct and the posterior segmental duct in the hilar area. However, three other variations have been found in which these segmental ducts do not form the right hepatic duct. Few anatomical variations have been identified in the left hepatic duct, but confusion arises because of the variations in the medial segment ducts (B4) which join the left hepatic duct at different sites. In 35.5% of individuals they join the hepatic duct in the vicinity of the hilar confluence (type I B4 anatomy), and in 64.5% of individuals they join the left hepatic duct some distance away from the confluence (type II B4 anatomy). Because B4 is very close to the hilar confluence in type I, hilar bile duct carcinoma can easily invade B4 and, for that reason, for curative resection of hilar bile duct carcinoma, resection of S4a (the inferior part of the medial segment) should be considered along with the resection of extrahepatic bile duct and caudate lobe. Variations in the portal vein and hepatic artery are found in 16%-26% and 31%-33% of individuals, respectively. Because a considerable number of anatomical variations in the bile ducts and vessels persist in the hilar area, and the reported proportions of the different variations vary, it is necessary to have a good knowledge of the plate system and the variations in the bile ducts and blood vessels in the hilar area to perform safe and curative surgery for hilar bile duct carcinoma.

Bile Ducts↗

Surgical anatomy of the bile duct branches of the medial segment (B4) of the liver in relation to hilar carcinoma.

In some patients, hilar bile duct carcinoma can easily spread to the bile duct branches of the caudate lobe (B1) as well as to the bile duct branches of the medial segment (B4), and resection of the inferior portion of the medial segment (S4a) is then required. It is therefore important to understand the detailed anatomy of the B4, its confluence patterns, and its relation to the B1 in order to be able to identify such patients. The confluence pattern of the B4 was studied in 141 specimens (68 adult cadavers and 73 liver casts) and the distance between the left bile duct branches of the caudate lobe (B11) and the B4 was measured in 56 of the 73 casts in which both B11 and B4 were present. Two main gross types of B4 were recognized: type I, in which B4 joined the left hepatic duct (LHD) close to the hilar confluence (35.5%), and type II, in which B4 joined the LHD far from the hilar confluence (54.6%). Analysis of the relationship between B11 and B4 revealed a mean distance between B11 and B4 of 8 mm in type 1, and 17 mm in type II. When the distance is less than 10 mm, B11 and B4 are considered to be located very close to each other, and in such individuals hilar bile duct carcinoma can infiltrate the B4 easily, thereby necessitating the resection of S4a, together with a caudate lobectomy for curative resection. Also, the confluence pattern of the B4 often creates a problem when the LHD is divided and reconstructed during hepatectomy, because of the numerous anatomical variations of the B4 itself. We therefore concluded that a good anatomical knowledge of the B4 and its relation to the B11 is essential in making the decision to perform S4a resection in selected patients with hilar bile duct carcinoma with the aim of curative resection.

Adult↗

Lazaroid reduces production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury.

BACKGROUND: 21-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral ischemic injury through the inhibition of lipid peroxidation. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in ischemic spinal cord injury model. MATERIALS: Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic cross-clamping (AXC) with pretreatment of either an intravenous 3 mg/kg lazaroid U74389G (group L; n = 10) or the same volume saline (group P; n = 10). Sham operation group (group S; n = 6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1beta, -1 receptor antagonist (IL-1ra) and tumor necrosis factor (TNF)-alpha were measured at four time points. Functional assessment with Tarlov score at 24 and 48 hours after pretreatment, pathologic assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed. RESULTS: The maximum elevation of plasma IL-8 and -1ra levels occurred at 1 hour after declamping in four measurement points. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p < 0.05). Plasma TNFalpha peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFalpha levels were not different among three groups. Spinal IL-8 levels in group L (0.98 +/- 0.34 ng/g tissue) were lower than those in group P (7.26 +/- 2.26 ng/g tissue)(*p < 0.05). Spinal IL-1ra and TNFalpha were not significantly different. Tarlov score and pathologic assessment were better in group L. CONCLUSIONS: Lazaroid U-74389G reduced the production of systemic IL-8 and -1ra and spinal IL-8 when AXC caused spinal cord injury. These results indicate that lazaroids may attenuate ischemic endothelial cell injury or activation of leukocytes.

Animals↗

Behavioral effect of mouse fibrinopeptide A on mouse forced swimming.

A specific dopamine 2 receptor antagonist, (-)sulpiride, induced an anti-depressive behavior, climbing, in mice forced to swim for 6 h after the injection. The effective fraction was divided from the mouse serum using an ion exchanger and an ultra filtration method. This fraction contained fibrinopeptide A. A peptide synthesized according to the primary 6-amino acid sequence (TDTEDK) of fibrinopeptide A also remarkably increased the behavior. The present findings clearly indicate that a peptide with TDTEDK showed anti-depressive activity.

Amino Acid Sequence↗

The role of sialylated Lewis antigens on hematogenous metastases of human pancreas carcinoma cell lines in vivo.

Previous studies have shown that sialyl Lewis a (SLea) and sialyl Lewis x (SLex) correlated to hematogenous metastasis of human cancers. Although SLea/SLex and E-selectin act as a set of adhesion molecules in vitro, it is not clear whether the in vivo correlation is exclusively mediated by the adhesion function. To address this issue, we investigated whether or not the role of SLea/SLex antigens on hematogenous metastasis to the liver in SCID mice was exclusively mediated by adhesion by using antibodies for these antigens and SLea/SLEx-negative, human pancreas adenocarcinoma cell line PCI-6. The absence of SLea/SLex expression was supported by the absent flow cytometric detection of the antigens as well as by the absent attachment augmentation to activated endothelial cells. PCI-6 cells are xenotransplantable to nude and SCID mice and produce vascular endothelial cell growth factor (VEGF) in a significant amount. PCI-6 cells, 1 x 10(6), were injected into the spleens of SCID mice, and resultant liver metastases were evaluated six weeks later. We observed an inhibitory effect on the establishment and growth of metastatic colonies when anti-SLea or anti-SLex antibody was administered. This indicates that SLea/x antigens have an important in vivo role, even in the metastasis of SLea/SLex-negative tumor cells. This implies that there may be an in vivo function of SLea/x antigens other than that of the attachment between tumor and endothelial cells.

Animals↗

Aortoesophageal fistula-relief of massive hematemesis with an endovascular stent-graft.

A 59-year-old man with an esophageal carcinoma developed massive hematemesis due to aortoesophageal fistula after irradiation therapy reached 58 Gy. Emergent treatment with an endovascular stent-graft was successfully performed and the patient followed an uneventful course until he died of pneumonia 4.5 months later, which was caused by a tracheoesophageal fistula. Stent-graft repair is a safe and effective method to treat aortoesophageal fistula and may be an alternative to surgical resection.

Aortic Diseases↗

Combination analysis of genetic alterations and cell proliferation in small intestinal carcinomas.

We analyzed K-ras and p53 mutations, microsatellite instability (MSI), and loss of heterozygosity (LOH) using the polymerase chain reaction (PCR) methods, as well as p53 expression and the Ki-67 labeling index (LI) using immunohistochemistry in 10 duodenal and 10 jejunal/ileal carcinomas. K-ras mutations were detected in two duodenal (20%) and three jejunal/ileal (30%) carcinomas and p53 mutations in one (10%) and three (30%), respectively. LOH of 17p was detected in two duodenal (20%) and two jejunal/ileal (20%) carcinomas and p53 expression in four duodenal (40%) and four jejunal/ileal (40%). One duodenal (10%) and two jejunal/ileal (20%) carcinomas demonstrated MSI. LOH of APC was detected in three jejunal/ileal (30%), but none of the duodenal carcinomas. The Ki-67 LI was 44% in duodenal and 52.6% in jejunal/ileal carcinomas. A subset of small intestinal carcinomas showed involvement of K-ras and p53 mutations, LOH of APC, and MSI. A difference was also apparent for LOH of APC between duodenal and jejunal/ileal carcinomas.

Adult↗

Analyses of matrix metalloproteinases and their inhibitors in cyst fluid of serous ovarian tumors.

OBJECTIVES: Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) in serous tumors of the ovary was investigated to determine whether and how these proteolytic enzymes are associated with the progression of these tumors. METHODS: Cyst fluid of 24 serous ovarian tumors (8 adenocarcinomas, 2 borderline tumors and 14 adenomas) was analyzed using gelatin/casein zymography and enzyme-linked immunosorbent assay. RESULTS: Concentrations of MMP-9 and MMP-2 were statistically higher in serous adenocarcinomas than in serous adenomas (p < 0.01, p < 0.05, respectively), while the concentrations of TIMP-1 and TIMP-2 showed no significant difference between adenocarcinomas and adenomas. The molar ratio of TIMP-2/MMP-2 was lower in adenocarcinomas than in adenomas (p < 0.05). With gelatin zymography, the MMP-9 band was detected in all serous adenocarcinomas, but only in 8 of 14 serous adenomas (p = 0.05). Using casein zymography, MMP-7 was more frequently detected in serous adenocarcinomas (7/8) than in serous adenomas (4/14; p < 0.05). CONCLUSIONS: These observations indicate that matriolytic enzymes such as MMP-2, MMP-7 and MMP-9 are secreted into cyst fluid from serous adenocarcinoma tissues. In part, the aggressive invasion of serous carcinoma cells may be explained by the expression of matriolytic enzymes.

Adenoma↗

Quantitative detection of apoptotic thymocytes in low-dose X-irradiated mice by an anti-single-stranded DNA antibody.

The quantitative detection of apoptotic cells in low frequency in the thymus of mice irradiated with X-rays using an anti-single-stranded DNA antibody was explored. The antibody against single-stranded DNA (anti-ssDNA) was obtained with rabbits hyperimmunized with complexes of alkaline-denatured calf thymus DNA. AKR female mice were irradiated with 10 to 100 cGy or 4 Gy X-rays; thereafter, thymus sections were prepared at various times after irradiation. The detection and counting of apoptotic cells in the section were performed after histochemical staining using an anti-ssDNA antibody. The results demonstrate that, although sensitive and quantitative detection of apoptotic cells in irradiated thymus using the anti-ssDNA antibody is possible, the sensitivity is lower compared to that of in situ end-labeling methods, such as TUNEL or ISEL. The antibodies could also be used for rat thymus and spleen. In addition, an increase in positively stained cells by both methods was detected as early as 6 min after the irradiation of mice.

Animals↗